POMALONG Capsules (Pomalidomide)

Table of Content

Pomalidomide is the most recent and potent immunomodulator (IMiD) molecule. It has redefined the therapeutic landscape for relapsed and refractory multiple myeloma (MM) patients. It is 100 times more potent than thalidomide. This observation has proved useful in the clinical setting as noted in the results from clinical trials in heavily pre-treated MM patients, including those resistant to lenalidomide or bortezomib (or both). Similar to prior experience with other IMiDs, the response to pomalidomide appears higher when combined with dexamethasone. The addition of a third agent (carfilzomib, clarithromycin or cyclophosphamide) to this combination has demonstrated improved efficacy in the overall response rate (ORR) with an acceptable toxicity profile.

Black Box Warning: Embryo-Foetal Toxicity and Venous and Arterial Thromboembolism

Embryo-Foetal Toxicity

  • Pomalong (pomalidomide) is contraindicated in pregnancy. Pomalidomide is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe life-threatening birth defects.
  • For females of reproductive potential: Exclude pregnancy before start of treatment. Prevent pregnancy during treatment using two reliable methods of contraception.

Venous and Arterial Thromboembolism

  • Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke are possible risks in patients with multiple myeloma treated with pomalidomide. Antithrombotic prophylaxis is recommended.

Composition

POMALONG 1 Capsules

Each capsule contains:

Pomalidomide........ 1 mg

Approved colours used in capsule shell

POMALONG 4 Capsules

Each capsule contains:

Pomalidomide ........ 4 mg

Approved colours used in capsule shell

Dosage Form

Oral capsule

Pharmacology

Pharmacodynamics

Mechanism of Action

Pomalidomide, an analogue of thalidomide, is an immunomodulatory agent with antineoplastic activity. In in vitro cellular assays, pomalidomide inhibited proliferation and induced apoptosis of haematopoietic tumour cells. Additionally, pomalidomide inhibited the proliferation of lenalidomide-resistant multiple myeloma cell lines and synergized with dexamethasone in both lenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumour cell apoptosis. Pomalidomide enhanced T cell- and natural killer (NK) cell-mediated immunity and inhibited production of pro-inflammatory cytokines (e.g. TNF-alpha and IL-6) by monocytes. Pomalidomide demonstrated anti-angiogenic activity in a mouse tumour model and in the in vitro umbilical cord model.

Pharmacokinetics

Absorption

With a single oral dose of pomalidomide, the maximum plasma concentration (Cmax) occurs at 2 and 3 hours post-dose. The systemic exposure (AUC) of pomalidomide increases in an approximately dose-proportional manner. In patients with multiple myeloma who received pomalidomide 4 mg daily alone or in combination with dexamethasone, pomalidomide, steady-state drug exposure was characterized by AUC(T) of 400 ng·h/mL and Cmax of 75 ng/mL. In multiple doses, pomalidomide has an accumulation ratio of 27% to 31%.

Distribution

Pomalidomide has a mean apparent volume of distribution (Vd/F) between 62 and 138 L at steady state. Pomalidomide is distributed in the semen of healthy subjects at a concentration of approximately 67% of plasma level at 4 hours post-dose (~Tmax) after 4 days of once-daily dosing at 2 mg. Human plasma protein-binding ranges from 12% to 44% and is not concentration-dependent. Pomalidomide is a substrate for P-glycoprotein (P-gp).

Metabolism and Excretion

Pomalidomide is primarily metabolized in the liver by CYP1A2 and CYP3A4. In vitro, CYP1A2 and CYP3A4 were identified as the primary enzymes involved in the CYP-mediated hydroxylation of pomalidomide, with additional minor contributions from CYP2C19 and CYP2D6.

Pomalidomide is eliminated with a median plasma half-life of approximately 9.5 hours in healthy subjects and approximately 7.5 hours in patients with multiple myeloma. Pomalidomide has a mean total body clearance (CL/F) of 7 to 10 L/h. A single oral administration of -pomalidomide (2 mg) to healthy subjects, approximately 73% and 15% of the radioactive dose was eliminated in urine and faeces, with approximately 2% and 8% of the radiolabelled dose eliminated unchanged as pomalidomide in urine and faeces.

Drug Interactions

The effect of CYP1A2 inhibitors, in the absence of a co-administered CYP3A4 and P-gp inhibitor, is unknown. However, co-administration of fluvoxamine (a strong CYP1A2 inhibitor) in the presence of ketoconazole (a strong CYP3A4 and P-gp inhibitor) to 12 healthy male subjects increased exposure (geometric mean AUCinf) to pomalidomide by 146% compared to pomalidomide administered alone.

Strong CYP3A4 and P-gp Inhibitors

Co-administration of ketoconazole (a strong CYP3A4 and P-gp inhibitor) in 16 healthy male subjects resulted in an increased AUC of pomalidomide of 19% compared with pomalidomide administered alone.

Drugs That Induce Pomalidomide Metabolism

Co-administration of pomalidomide with drugs that are CYP1A2 inducers has not been studied and may reduce pomalidomide exposure.

Dexamethasone

Co-administration of multiple doses of 4 mg pomalidomide with 20 mg to 40 mg dexamethasone (a weak-to-moderate inducer of CYP3A4) to patients with multiple myeloma had no effect on the pharmacokinetics of pomalidomide compared with pomalidomide administered alone.

In Vitro Inhibition of Drug-metabolizing Enzymes and Transporters by Pomalidomide

Pomalidomide does not inhibit or induce CYP450 enzymes or transporters in vitro.

Special Populations

Renal Impairment

Pomalidomide and its metabolites are primarily excreted by the kidneys. The influence of renal impairment on the safety, efficacy and pharmacokinetics of pomalidomide has not been evaluated. Avoid pomalidomide in patients with a serum creatinine greater than 3.0 mg/dL.

Hepatic Impairment

Pomalidomide is metabolized in the liver. The influence of hepatic impairment on the safety, efficacy and pharmacokinetics of pomalidomide has not been evaluated. Avoid pomalidomide in patients with serum bilirubin greater than 2.0 mg/dL and AST/ALT greater than 3.0 × ULN.

Geriatric

No dosage adjustment is required for pomalidomide based on age. No overall differences in effectiveness were observed between these patients and younger patients. Patients older than 65 years were more likely than patients less than or equal to 65 years of age to experience pneumonia.

Paediatric

Safety and effectiveness of pomalidomide in patients below the age of 18 years have not been established.

Indications

Multiple Myeloma

POMALONG Capsules (pomalidomide), in combination with dexamethasone, are indicated for patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on or within 60 days of completion of the last therapy.

Dosage and Administration

Multiple Myeloma

Females of reproductive potential must have negative pregnancy testing and use contraception methods before initiating pomalidomide. The recommended starting dose of pomalidomide is 4 mg once daily orally on days 1 to 21 of repeated 28-day cycles until disease progression. Pomalidomide should be given in combination with dexamethasone. Pomalidomide may be taken with water. Inform patients not to break, chew, or open the capsules. Pomalidomide should be taken without food (at least 2 hours before or 2 hours after a meal).

Dose Adjustments for Toxicities

Table 1: Dose modification for POMALONG Capsules (pomalidomide) for haematologic toxicities

Toxicity

Dose modification

Neutropaenia

ANC <500 per mcL or febrile neutropaenia (fever more than or equal to 38.5°C and ANC <1,000 per mcL)

ANC return to more than or equal to 500 per mcl

For each subsequent drop <500 per mcL

Return to more than or equal to 500 per mcL

 

Interrupt pomalidomide treatment, follow CBC weekly.

Resume pomalidomide treatment at 3 mg daily

Interrupt pomalidomide treatment

Resume pomalidomide treatment at 1 mg less than the previous dose

Thrombocytopaenia

Platelets <25,000 per mcL

Platelets return to >50,000 per mcL

For each subsequent drop <25,000 per mcL

Return to more than or equal to 50,000 per mcL

 

Interrupt pomalidomide treatment, follow CBC weekly

Platelets return to >50,000 per mcL

Interrupt pomalidomide treatment

Resume pomalidomide treatment at 1 mg less than previous dose

To initiate a new cycle of pomalidomide, the neutrophil count must be at least 500 per mcL and the platelet count must be at least 50,000 per mcL. If toxicities occur after dose reductions to 1 mg, then discontinue pomalidomide. Permanently discontinue pomalidomide for angio-oedema, skin exfoliation, bullae, or any other severe dermatologic reaction. For other Grade 3 or 4 toxicities, hold treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to less than or equal to Grade 2 at the physician’s discretion.

Dose Adjustment for Strong CYP1A2 Inhibitors in the Presence of Strong CYP3A4 and P-gp Inhibitors

Avoid co-administration of strong inhibitors of CYP1A2. If necessary to co-administer strong inhibitors of CYP1A2 in the presence of strong inhibitors of CYP3A4 and P-gp, reduce pomalidomide dose by 50%. Clinical efficacy or safety data exist is unavailable.

Special Populations

Paediatric Use

Safety and effectiveness of pomalidomide in patients below the age of 18 years have not been established.

Geriatric Use

No dosage adjustment is required for pomalidomide based on age. No overall differences in effectiveness were observed between these patients and younger patients. Patients older than 65 years were more likely than patients less than or equal to 65 years of age to experience pneumonia.

Patients with Hepatic Impairment

Lenalidomide has not formally been studied in patients with impaired hepatic function and there are no specific dose recommendations.

Females of Reproductive Potential and Males

Pomalidomide can cause foetal harm when administered during pregnancy. Females of reproductive potential must avoid pregnancy while taking pomalidomide and for at least 4 weeks after completing therapy.

Contraindications

Pregnancy Category X

Pomalidomide can cause foetal harm when administered to a pregnant female. Pomalidomide is contraindicated in females who are pregnant. Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a foetus.

Warnings and Precautions

Drug Interactions

Pomalidomide is primarily metabolized by CYP1A2 and CYP3A. Pomalidomide is also a substrate for P-gp.

Drugs That May Increase Pomalidomide Plasma Concentrations

CYP1A2 Inhibitors

Pomalidomide exposure is increased when pomalidomide is co-administered with a strong CYP1A2 inhibitor (fluvoxamine) in the presence of a strong CYP3A4/5 and P-gp inhibitor (ketoconazole). Ketoconazole in the absence of a CYP1A2 inhibitor does not increase pomalidomide exposure. Avoid co-administration of strong CYP1A2 inhibitors (e.g. ciprofloxacin and fluvoxamine). If it is medically necessary to co-administer strong inhibitors of CYP1A2 in the presence of strong inhibitors of CYP3A4 and P-gp, pomalidomide dose should be reduced by 50%. The effect of a CYP1A2 inhibitor in the absence of a co-administered CYP3A4 and P-gp inhibitor has not been studied. Monitor for toxicities if CYP1A2 inhibitors are to be co- administered in the absence of a co-administered CYP3A4 and P-gp inhibitor, and reduce dose if needed.

Drugs That May Decrease Pomalidomide Plasma Concentrations

Smoking

Cigarette smoking may reduce pomalidomide exposure due to CYP1A2 induction. Patients should be advised that smoking may reduce the efficacy of pomalidomide.

CYP1A2 Inducers

Co-administration of pomalidomide with drugs that are CYP1A2 inducers has not been studied and may reduce pomalidomide exposure.

Embryo-Foetal Toxicity

Pomalidomide is a thalidomide analogue and is contraindicated for use during pregnancy. Thalidomide is a known human teratogen that causes severe birth defects or embryo-foetal death.

Females

Females of reproductive potential must avoid pregnancy while taking pomalidomide and for at least 4 weeks after completing therapy. Females must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control, beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of pomalidomide therapy. Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed within 10 to 14 days and the second test within 24 hours prior to prescribing pomalidomide therapy and then weekly during the first month, then monthly thereafter in women with regular menstrual cycles, or every 2 weeks in women with irregular menstrual cycles.

Males

Pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking pomalidomide and for up to 28 days after discontinuing pomalidomide, even if they have undergone a successful vasectomy. Male patients taking pomalidomide must not donate sperm.

Blood Donation

Patients must not donate blood during treatment with pomalidomide and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose foetus must not be exposed to pomalidomide.

Venous and Arterial Thromboembolism

Venous thromboembolic events (deep venous thrombosis and pulmonary embolism) and arterial thromboembolic events (myocardial infarction and stroke) have been observed in patients treated with pomalidomide. Patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to try to minimize all modifiable factors (e.g. hyperlipidaemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors.

Haematologic Toxicity

Monitor patients for haematologic toxicities, especially neutropaenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.

Hepatotoxicity

Hepatic failure, including fatal cases, has occurred in patients treated with pomalidomide. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with pomalidomide. Monitor liver function tests monthly. Stop pomalidomide upon elevation of liver enzymes and evaluate. After return to baseline values, treatment at a lower dose may be considered.

Hypersensitivity Reactions

Angio-oedema and severe dermatologic reactions have been reported. Discontinue pomalidomide for angio-oedema, skin exfoliation, bullae, or any other severe dermatologic reactions, and do not resume therapy.

Dizziness and Confusional State

Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice.

Neuropathy

In clinical trials with patients who received pomalidomide + low-dose dexamethasone, 18% of patients experienced neuropathy, with approximately 12% of the patients experiencing peripheral neuropathy. Up to 2% of patients experienced Grade 3 neuropathy. There were no cases of Grade 4 neuropathy adverse reactions reported in the trials.

Risk of Second Primary Malignancies

Second primary malignancies have been reported in patients receiving pomalidomide. Physicians should carefully evaluate patients before and during treatment, using standard cancer screening for the occurrence of second primary malignancies.

Tumour Lysis Syndrome

Tumour lysis syndrome (TLS) may occur in patients treated with pomalidomide. Patients at risk for TLS are those with high tumour burden prior to treatment. These patients should be monitored for occurrence closely and appropriate precautions taken.

Undesirable Effects

Clinical Trials Experience

In Trial 1, data were evaluated from 219 patients (safety population) who received treatment with pomalidomide + low-dose dexamethasone (112 patients) or pomalidomide alone (107 patients). Median number of treatment cycles was 5. Up to 67% of patients in the study had a dose interruption of either drug due to adverse reactions. Nearly 42% of patients in the study had a dose reduction of either drug due to adverse reactions. The discontinuation rate due to adverse reactions was 11%.

In Trial 2, data were evaluated from 450 patients (safety population) who received treatment with pomalidomide + low-dose dexamethasone (300 patients) or high-dose dexamethasone (150 patients). The median number of treatment cycles for the pomalidomide + low-dose dexamethasone arm was 5.

In the pomalidomide + low-dose dexamethasone arm, 67% of patients had a dose interruption of pomalidomide, the median time to the first dose interruption of pomalidomide was 4.1 weeks.

Up to 27% of patients had a dose reduction of pomalidomide, the median time to the first dose reduction of pomalidomide was 4.5 weeks. Also, 8% of patients discontinued pomalidomide due to adverse reactions.

Tabulated List of Adverse Reactions

Table 2: Adverse reactions observed with pomalidomide treatment, pomalidomide + low-dose dexamethasone and adverse reactions in any pomalidomide treatment arm in trial 1
 

All adverse reactions ≥10% in all treatment regimens

Grade 3 to 4, ≥5% in all treatment regimens

System organ class/ preferred term

Pomalidomidea (N=107)

Pomalidomide + low-dose dexamethasone (N=112)

Pomalidomide (N=107)

Pomalidomide + low-dose dexamethasone (N=112)

Blood and lymphatic system disorders

 

 

Neutropaeniab

57 (53.3)

55 (49.1)

51 (47.7)

46 (41.1)

Anaemiab

41 (38.3)

47 (42.0)

25 (23.4)

24 (21.4)

Thrombocytopaeniab

28 (26.2)

26 (23.2)

24 (22.4)

21 (18.8)

Leucopaeniab

14 (13.1)

22 (19.6)

7 (6.5)

11 (9.8)

Febrile neutropaeniab

<10%

<10%

6 (5.6)

3 (2.7)

Lymphopaenia

4 (3.7)

17 (15.2)

2 (1.9)

8 (7.1)

General disorders and administration site conditions

 

 

Fatigue and astheniab

62 (57.9)

70 (62.5)

13 (12.1)

19 (17.0)

Oedema peripheral

27 (25.2)

19 (17.0)

0 (0.0)

0 (0.0)

Pyrexiab

25 (23.4)

36 (32.1)

<5%

<5%

Chills

11 (10.3)

14 (12.5)

 0 (0.0)

0 (0.0)

Gastrointestinal disorders

 

 

Nauseab

39 (36.4)

27 (24.1)

<5%

<5%

Constipationb

38 (35.5)

41 (36.6)

<5%

<5%

Diarrhoea

37 (34.6)

40 (35.7)

<5%

<5%

Vomitingb

15 (14.0)

16 (14.3)

 <5%

0 (0.0)

Musculoskeletal and connective tissue disorders

 

 

Back painb

37 (34.6)

36 (32.1)

15 (14.0)

11 (9.8)

Musculoskeletal chest pain

25 (23.4)

22 (19.6)

 <5%

0 (0.0)

Muscle spasms

23 (21.5)

22 (19.6)

<5%

<5%

Arthralgia

18 (16.8)

17 (15.2)

<5%

<5%

Muscular weakness

15 (14.0)

15 (13.4)

6 (5.6)

4 (3.6)

Bone pain

13 (12.1)

8 (7.1)

<5%

<5%

Musculoskeletal pain

13 (12.1)

19 (17.0)

<5%

<5%

Pain extremity

8 (7.5)

16 914.3)

0 (0.0)

<5%

Infections and infestation

 

 

Upper respiratory tract infection

40 (37.4)

32 (28.6)

<5%

<5%

Pneumoniab

30 (28.0)

38 (33.9)

21 (19.6)

32 (28.6)

Urinary tract infectionb

11 (10.3)

19 (17.0)

2 (1.9)

10 (8.9)

Sepsisb

<10%

<10%

6 (5.6)

5 (4.5)

Metabolism and nutrition disorders

 

 

Decreased appetite

25 (23.4)

21 (18.8)

<5%

0 (0.0)

Hypercalcaemiab

23 (21.5)

13 (11.6)

11 (10.3)

1 (0.9)

Hypokalaemia

13 (12.1)

13 (11.6)

<5%

<5%

Hyperglycaemia

12 (11.2)

17 (15.2)

<5%

<5%

Hyponatraemia

12 (11.2)

14 (12.5)

<5%

<5%

Dehydrationb

<10%

<10%

5 (4.7)

6 (5.4)

Hypocalcaemia

6 (5.6)

13 (11.6)

0 (0.0)

<5%

Respiratory, thoracic and mediastinal disorders

 

 

Dyspnoeab

38 (35.5)

50 (44.6)

8 (7.5)

14 (12.5)

Cough

18 (16.8)

25 (22.3)

0 (0.0)

0 (0.0)

Epistaxis

18 (16.8)

12 (10.7)

<5%

0 (0.0)

Predictive cough

10 (9.3)

14 (12.5)

0 (0.0)

0 (0.0)

Oropharyngeal pain

6 (5.6)

12 (10.7)

0 (0.0)

0 (0.0)

Nervous system disorders

 

 

Dizziness

24 (22.4)

20 (17.9)

<5%

<5%

Peripheral neuropathy

23 (21.5)

20 (17.9)

0 (0.0)

0 (0.0)

Headache

16 (15.0)

15 (13.4)

0 (0.0)

<5%

Tremor

11 (10.3)

15 (13.4)

0 (0.0)

0 (0.0)

Skin and subcutaneous tissue disorders

 

 

Rash

22 (20.6)

18 (16.1)

0 (0.0)

<5%

Pruritus

16 (15.0)

10 (8.9)

0 (0.0)

0 (0.0)

Dry skin

10 (9.3)

12 (10.7)

0 (0.0)

0 (0.0)

Hyperhidrosis

8 (7.5)

18 (16.1)

0 (0.0)

0 (0.0)

Night sweats

5 (4.7)

14 (12.5)

0 (0.0)

0 (0.0)

Investigations

 

 

Blood creatinine increasedb

20 (18.7)

11 (9.8)

6 (5.6)

3 (2.7)

Weight decreased

16 (15.0)

10 (8.9)

0 (0.0)

0 (0.0)

Weight increased

1 (0.9)

12 (10.7)

0 (0.0)

0 (0.0)

Psychiatric disorders

 

 

 

 

Anxiety

14 (13.1)

8 (7.1)

0 (0.0)

0 (0.0)

Confusional stateb

13 (12.1)

15 (13.4)

6 (5.6)

3 (2.7)

Insomnia

7 (6.5)

18 (16.1)

0 (0.0)

0 (0.0)

Renal and urinary disorders

 

 

Renal failureb

16 (15.0)

11 (9.8)

9 (8.4)

8 (7.1)

a Pomalidomide alone arm includes all patients randomized to the pomalidomide alone arm who took the study drug; 61 of the 107 patients had dexamethasone added during the treatment period.

b Serious adverse reactions were reported in at least 2 patients in any pomalidomide treatment arm. Data cutoff: 01 March 2013

Table 3: Adverse reactions in trial 2*

 

All adverse reactions (≥5% in pomalidomide + low-dose dexamethasone arm, and at least 2% point higher than the high-dose dexamethasone arm)

Grade 3 or 4 (≥1% in pomalidomide + low-dose dexamethasone arm, and at least 1% point higher than the high-dose dexamethasone arm)

System organ class/ Preferred term

Pomalidomide + low-dose dexamethasone (N=300)

High-dose

dexamethasone (N=150)

Pomalidomide

+ low-dose

dexamethasone (N=300)

High-dose dexamethasone

(N=150)

Number (%) of patients with at least one adverse reaction

297 (99.0)

149 (99.3)

259 (86.3)

127 (84.7)

Blood and lymphatic system disorders

 

 

 

 

Neutropaenia b

154 (51.3)

31 (20.7)

145 (48.3)

24 (16.0)

Thrombocytopaenia

89 (29.7)

44 (29.3)

66 (22.0)a

39 (26.0)a

Leucopaenia

38 (12.7)

8 (5.3)

27 (9.0)

5 (3.3)

Febrile neutropaeniab

28 (9.3)

0 (0.0)

28 (9.3)

0 (0.0)

General disorders and administration site conditions

 

 

 

 

Fatigue and asthenia

140 (46.7)

64 (42.7)

26 (8.7) a

18 (12.0) a

Pyrexiab

80 (26.7)

35 (23.3)

9 (3.0)a

7 (4.7) a

Oedema peripheral

52 (17.3)

17 (11.3)

4 (1.3) a

3 (2.0) a

Pain

11 (3.7) a

3 (2.0) a

5 (1.7)

1 (0.7)

Infections and infestations

 

 

Upper respiratory tract infectionb

93 (31.0)

19 (12.7)

9 (3.)

1 (0.7)

Pneumoniab

58 (19.3)

20 (13.3)

47 (15.7)

15 (10.0)

Neutropenic sepsisb

3 (1.0)a

0 (0.0)a

3 (1.0)

0 (0.0)

Gastrointestinal disorders

 

 

 

 

Diarrhoea

66 (22.0)

28 (18.7)

3 (1.0) a

2 (1.3) a

Constipation

65 (21.7)

22 (14.7)

7 (2.3)

0 (0.0)

Nausea

45 (15.0)

17 (11.3)

3 (1.0) a

2 (1.3) a

Vomiting

23 (7.7)

6 (4.0)

3 (1.0)

0 (0.0)

Musculoskeletal and connective tissue disorders

 

 

 

 

Back painb

59 (19.7)

24 (16.0)

15 (5.0)

6 (4.0)

Bone painb

54 (18.0)

21 (14.0)

22 (7.3)

7 (4.7)

Muscle spasms

46 (15.3)

11 (7.3)

1 (0.3)a

1 (0.7)a

Arthralgia

26 (8.7)

7 (4.7)

2 (0.7)

1 (0.7)

Pain in extremity

20 (6.7)a

9 (6.0)a

6 (2.0)

0 (0.0)

Respiratory, thoracic and mediastinal disorders

 

 

Dyspnoeab

76 (25.3)

25 (16.7)

17 (5.7)

7 (4.7)

Cough

60 (20.0)

15 (10.0)

2 (0.7)a

1 (0.7)a

Chronic obstructive pulmonary diseaseb

5 (1.7)a

0 (0.0)a

4 (1.3)

0 (0.0)

Nervous system Disorders

 

 

Peripheral neuropathy

52 (17.3)

18 (12.0)

5 (1.7)a

2 (1.3)a

Dizziness

37 (12.3)

14 (9.3)

4 (1.3)a

2 (1.3)a

Headache

23 (7.7)

8 (5.3)

1 (0.3)a

0 (0.0)a

Tremor

17 (5.7)

2 (1.3)

2 (0.7)a

0 (0.0)a

Depressed level of

consciousness

5 (1.7)a

0 (0.0)a

3 (1.0)

0 (0.0)

Metabolism and nutrition disorders

 

 

 

 

Decreased appetite

38 (12.7)

12 (8.0)

3 (1.0)a

2 (1.3)a

Hypokalaemia

28 (9.3)a

12 (8.0)a

12 (4.0)

4 (2.7)

Hypocalcaemia

12 (4.0)a

9 (6.0)a

5 (1.7)

1 (0.7)

Skin and subcutaneous tissue disorders

 

 

Rash

23 (7.7)

2 (1.3)

3 (1.0)

0 (0.0)

Pruritus

22 (7.3)

5 (3.3)

0 (0.0)a

0 (0.0)a

Hyperhidrosis

15 (5.0)

1 (0.7)

0 (0.0)a

0 (0.0)a

Investigations

 

 

Neutrophil count

decreased

15 (5.0)

1 (0.7)

14 (4.7)

1 (0.7)

Platelet count

decreased

10 (3.3)a

3 (2.0)a

8 (2.7)

2 (1.3)

White blood cell count

decreased

8 (2.7)a

1 (0.7)a

8 (2.7)

0 (0.0)

Alanine aminotransferase

increased

7 (2.3)a

2 (1.3)a

5 (1.7)

0 (0.0)

Aspartate aminotransferase

increased

4 (1.3)a

2 (1.3)a

3 (1.0)

0 (0.0)

Lymphocyte count

decreased

3 (1.0)a

1 (0.7)a

3 (1.0)

0 (0.0)

Renal and urinary

Disorders

 

 

 

 

Renal failure

31 (10.3)a

18 (12.0)a

19 (6.3)

8 (5.3)

Injury, poisoning and Procedural complications

 

 

Femur fracture

5 (1.7)a

1 (0.7)a

5 (1.7)

1 (0.7)

Reproductive system and breast disorders

 

 

Pelvic pain

6 (2.0)a

3 (2.0)a

4 (1.3)

0 (0.0)

a Percentage did not meet the criteria to be considered as an adverse reaction for pomalidomide for that category of event (i.e. all adverse events or Grade 3 or 4 adverse events).

b Serious adverse reactions were reported in at least 3 patients in the pomalidomide + low-dose dexamethasone arm, and at least 1% higher than the high-dose dexamethasone arm percentage.

Data cutoff: 01 March 2013

Other Adverse Reactions

Other adverse reactions of pomalidomide in patients with multiple myeloma were as follows:

Cardiac Disorders: Myocardial infarction, atrial fibrillation, angina pectoris, cardiac failure congestive.

Ear and Labyrinth Disorders: Vertigo.

Gastrointestinal Disorders: Abdominal pain.

General Disorders and Administration Site Conditions: General physical health deterioration, non-cardiac chest pain, multi-organ failure.

Hepatobiliary Disorders: Hyperbilirubinaemia.

Infections and Infestations: Pneumocystis jirovecii pneumonia, respiratory syncytial virus infection, neutropaenic sepsis, bacteraemia, pneumonia respiratory syncytial viral, cellulitis, urosepsis, septic shock, Clostridium difficile colitis, pneumonia streptococcal, lobar pneumonia, viral infection, lung infection.

Investigations: Alanine aminotransferase increased, haemoglobin decreased.

Injury, Poisoning and Procedural Complications: Fall, compression fracture, spinal compression, fracture.

Metabolism and Nutritional Disorders: Hyperkalaemia, failure to thrive.

Nervous System Disorders: Depressed level of consciousness, syncope.

Psychiatric Disorders: Mental status change.

Renal and Urinary Disorders: Urinary retention, hyponatraemia.

Reproductive System and Breast Disorders: Pelvic pain.

Respiratory, Thoracic and Mediastinal Disorders: Interstitial lung disease, pulmonary embolism, respiratory failure, bronchospasm.

Vascular Disorders: Hypotension.

Overdosage

No specific information is available on the treatment of overdose with pomalidomide, and it is unknown whether pomalidomide or its metabolites are dialysable. In the event of overdose, supportive care should be advised by physician.

Incompatibility

Not applicable.

Shelf-Life

2 years

Storage and Handling Instructions

Store below 25°C.

Pomalidomide capsules should not be opened or crushed. If powder from pomalidomide contacts the skin, wash the skin immediately and thoroughly with soap and water. If pomalidomide contacts the mucous membranes, flush thoroughly with water.

Packaging Information

POMALONG 1 Capsule
POMALONG 4 Capsules

Last updated: June 2017
Last reviewed: June 2017